Development of acid-amplifying polymers

Aguilar-Romero, Jazmin Emilia

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https://hdl.handle.net/2142/122190 Copy

Description

Title

Development of acid-amplifying polymers

Author(s)

Aguilar-Romero, Jazmin Emilia

Issue Date

2023-08-03

Director of Research (if dissertation) or Advisor (if thesis)

Zimmerman, Steve C

Doctoral Committee Chair(s)

Zimmerman, Steve C

Committee Member(s)

• Leal, Cecilia
• Guironnet, Damien
• Han, Hee-Sun

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• degradable polymers
• drug delivery

Abstract

Polymeric drug delivery systems have been explored extensively as vehicles to selectively transport small molecules, proteins, and other cargo. Although drug delivery systems have demonstrated advantages, such as decreased drug toxicity and stabilization of sensitive cargo, most polymers still face the issue of endosomal entrapment. Not escaping the endosome prevents drug delivery vehicles from releasing their contents into target sites. Various strategies have been developed to probe the mechanism of and promote endosomal escape with limited success. In this dissertation, I report the design of acid-amplifying small molecules and polymers for use in drug delivery to promote endosomal escape. Acid amplifiers were primarily utilized for applications in photolithography and photoresists. Although their properties can benefit pH-responsive drug delivery systems, acid amplifiers have remained largely untapped for biological applications. Additionally, most previously reported acid amplifiers require extensive heating for activation and produce acutely toxic byproducts. Chapter 2 investigates the design, synthesis, and studies of a novel acid amplifier that can be degraded at room temperature for use in drug delivery. The acid amplifier contains an acetal group that is hydrolyzed under acidic conditions to enable a quinone methide elimination that produces HCl. The degradation of the acid amplifier was monitored with 1H NMR and pH studies, which demonstrated rapid exponential conversion of the acid amplifier and an exponential drop in pH in physiologically relevant conditions. To incorporate the acid amplifier into polymers, RAFT and ROMP polymers were synthesized with side chains containing the acid amplifier. Chapter 3 describes the synthesis of these polymers and further studies. A ROMP copolymer with acid amplifier and a hydrophilic copolymer demonstrated an exponential drop in pH in fully aqueous acidic conditions at room temperature, improving upon a previously developed acid-amplifying polymers that required heating. In Chapter 4, I change topics to focus on the application of acid amplifiers to form degradable ROMP polymers for robust materials. A cyclooctene iodoacetal was synthesized and successfully polymerized via ROMP to form linear polyolefins. The acetals in the linear polymer fully hydrolyzed within 2 h in mixed aqueous organic solvent at 90 °C. Additionally, the cyclooctene iodocetal monomer was successfully copolymerized with cyclooctadiene, supporting that the acid amplifying monomer could be used to form a range of polymers.

Graduation Semester

2023-12

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Jazmin Aguilar-Romero

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